Mitochondrial governance of antitumour immunity: mechanisms and therapeutic exploration

Mitochondria are core regulators of cellular energy metabolism and signaling, and they play dual roles in tumorigenesis and antitumor immunity. Recent studies have shown that mitochondria modulate tumor cell immunogenicity and reshape the TME in an indispensable way. Tumor cells can evade immune surveillance, by virtue of abnormal mitochondrial metabolism, particularly the Warburg effect, and mutations in mtDNA. In turn, mitochondria also govern the function of immune cells, including T cell exhaustion and macrophage polarization, which further promotes tumor immune evasion. Importantly, mitochondria associated molecules such as mtROS and mtDAMPs can enhance antitumor immune responses by activating the innate cGAS–STING pathway, which is helpful for immunotherapy development. Here, we systematically analyse the molecular networks where mitochondria regulate tumor immunity. We indicate that targeting mitochondrial metabolism, mtDNA, mitochondrial quality control, mitochondrial transfer, combined with ICIs, holds great promise. We also explore the potential applications of mitochondrial biomarkers in antitumor immunity. These will establish a theoretical foundation for the development of novel immunotherapy strategies for tumor.